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Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers.

ABSTRACT: Chemotherapy resistance is a huge barrier for head and neck cancer (HNC) patients and therefore requires close attention to understand its underlay mechanisms for effective strategies. In this review, we first summarize the molecular mechanisms of chemotherapy resistance that occur during the treatment with cisplatin, 5-fluorouracil, and docetaxel/paclitaxel, including DNA/RNA damage repair, drug efflux, apoptosis inhibition, and epidermal growth factor receptor/focal adhesion kinase/nuclear factor-κB activation. Next, we describe the potential approaches to combining conventional therapies with previous cancer treatments such as immunotherapy, which may improve the treatment outcomes and prolong the survival of HNC patients. Overall, by parsing the reported molecular mechanisms of chemotherapy resistance within HNC patient's tumors, we can improve the prediction of chemotherapeutic responsiveness, and reveal new therapeutic targets for the future.

SUBMITTER: Kanno Y

PROVIDER: S-EPMC8138159 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers.

Kanno Yuzuka Y Chen Chang-Yu CY Lee Hsin-Lun HL Chiou Jeng-Fong JF Chen Yin-Ju YJ

Frontiers in oncology 20210507

Chemotherapy resistance is a huge barrier for head and neck cancer (HNC) patients and therefore requires close attention to understand its underlay mechanisms for effective strategies. In this review, we first summarize the molecular mechanisms of chemotherapy resistance that occur during the treatment with cisplatin, 5-fluorouracil, and docetaxel/paclitaxel, including DNA/RNA damage repair, drug efflux, apoptosis inhibition, and epidermal growth factor receptor/focal adhesion kinase/nuclear fac ...[more]

PMID: 34026617

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Project description:This review focuses on the molecular biology of head and neck squamous cell carcinomas and presents current and emerging biomarkers of the response of patients to induction chemotherapy. The usefulness of genes, proteins, and parameters from diagnostic clinical imaging as well as other clinicopathological parameters is thoroughly discussed. The role of induction chemotherapy before radiotherapy or before chemo-radiotherapy is still debated, as the data on its efficacy are somehow confusing. Despite the constant improvement of treatment protocols and the introduction of new cytostatics, there is still no consensus regarding the use of induction chemotherapy in the treatment of head and neck cancer, with the possible exception of larynx preservation. Such difficulties indicate that potential future treatment strategies should be personalized. Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Early prediction of treatment outcome or its toxicity may be highly beneficial for those who are at risk of the development of severe toxicities or treatment failure-a different treatment strategy may be applied to these patients, sparing them unnecessary pain. The literature search was carried out in the PubMed and ScienceDirect databases as well as in the selected conference proceedings repositories. Of the 265 articles and abstracts found, only 30 met the following inclusion criteria: human studies, analyzing prediction of induction chemotherapy outcome or toxicity based on the pretreatment (or after the first cycle, if more cycles of induction were administered) data, published after the year 2015. The studies regarding metastatic and recurrent cancers as well as the prognosis of overall survival or the outcome of consecutive treatment were not taken into consideration. As revealed from the systematic inspection of the papers, there are over 100 independent parameters analyzed for their suitability as prognostic markers in HNSCC patients undergoing induction chemotherapy. Some of them are promising, but usually they lack important features such as high specificity and sensitivity, low cost, high positive predictive value, clinical relevance, short turnaround time, etc. Subsequent studies are necessary to confirm the usability of the biomarkers for personal medicine.

Project description:BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32-71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Dataset Information

Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers.

Publications

Molecular Mechanisms of Chemotherapy Resistance in Head and Neck Cancers.

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